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- Title
ModM DNA methyltransferase methylome analysis reveals a potential role for Moraxella catarrhalis phasevarions in otitis media.
- Authors
Blakeway, Luke V.; Power, Peter M.; Jen, Freda E.-C.; Worboys, Sam R.; Boitano, Matthew; Clark, Tyson A.; Korlach, Jonas; Bakaletz, Lauren O.; Jennings, Michael P.; Peak, Ian R.; Seib, Kate L.
- Abstract
Moraxella catarrhalis is a significant cause of otitis media and exacerbations of chronic obstructive pulmonary disease. Here, we characterize a phase-variable DNA methyltransferase (ModM), which contains 5'-CAAC-3' repeats in its open reading frame that mediate high-frequency mutation resulting in reversible on/off switching of ModM expression. Three modM alleles have been identified (modM1-3), with modM2 being the most commonly found allele. Using single-molecule, real-time (SMRT) genome sequencing and methylome analysis, we have determined that the ModM2 methylation target is 5'-GARm6AC-3', and 100% of these sites are methylated in the genome of the M. catarrhalis 25239 ModM2 on strain. Proteomic analysis of ModM2 on and off variants revealed that ModM2 regulates expression of multiple genes that have potential roles in colonization, infection, and protection against host defenses. Investigation of the distribution of modM alleles in a panel of M. catarrhalis strains, isolated from the nasopharynx of healthy children or middle ear effusions from patients with otitis media, revealed a statistically significant association of modM3 with otitis media isolates. The modulation of gene expression via the ModM phase-variable regulon (phasevarion), and the significant association of the modM3 allele with otitis media, suggests a key role for ModM phasevarions in the pathogenesis of this organism.
- Subjects
DNA methyltransferases; MORAXELLA catarrhalis; OTITIS media; OBSTRUCTIVE lung diseases; GENETIC mutation
- Publication
FASEB Journal, 2014, Vol 28, Issue 12, p5197
- ISSN
0892-6638
- Publication type
Article
- DOI
10.1096/fj.14-256578